Blood flow

ABSTRACT

A provision of improving the flow of blood through a region of increased impedance is disclosed. The provision comprises assisting blood flow is said region by means of a pump placed in or around a blood vessel supplying blood to said area, and acting to pump blood in the required direction. The pump (1) comprises, in one embodiment, a housing (2) annularly surrounding a compressible conduit (3), said housing (2) containing a plurality of flexible inflatable containers (4) mounted for contact with said conduit (3) (e.g. a blood vessel) and means for effecting sequential inflation and deflation of said containers (4) so as to create a peristaltic pumping effect.

This invention relates to techniques and apparatus for improving bloodflow in vivo. The invention finds application in both clinical andveterinary practice.

Numerous problems arise from localised impedance to blood flow in bothhumans and non-human animals. For example, arterial damage, e.g.atherosclerosis, in the leg often requires complex surgery in which,typically, the long saphenous vein is used as a graft to by-pass thenon-functional arterial region. Also, cirrhosis of the liver, which mayresult from alcohol abuse in the western world but which is widespreadin the third world as a result of vital hepatitis, results in animpedance to blood flow from the hepatic portal vein into the liver.This results in blood by-passing the liver through portal veintributaries which feed into the stomach. This results in bleeding fromthe stomach wall (i.e. oesophageal varices).

The conventional treatment for this condition takes several forms: theblood pressure may be relieved by surgically forming a porto-systemicshunt such as a porto-caval shunt, in which the portal vein is connectedto the vena cava; or sclerotherapy may be used, in which the portal veintributaries are closed off by an appropriate injection. Otherconventional treatments are oesophageal transaction, in which the portalvein tributaries are closed off by appropriate sutures; and livertransplantation. These various treatments have various advantages anddisadvantages and, in some circumstances, may be of limited value.Sclerotherapy and oesophageal transection may not be effective over along period of time because the portal pressure (i.e. the blood pressurein the portal vein) is not reduced and often causes a recurrence ofbleeding, and a porto-caval shunt leads to most of the products absorbedby the gastro-intestinal tract passing directly into the general bloodcirculation, instead of travelling first to the liver where extensivemetabolic processes, in particular detoxification processes, take place.This decrease in blood flow through the liver reduces the effectivenessof this organ, particularly in its detoxifying capacity. This in turncan lead to serious side effects such as hepatic encephalopathy.

It will be appreciated from the above examples that standard treatmentfor a localised impedance to blood flow is to provide some means wherebyblood can by-pass the obstruction, thereby removing the localisedhypertension, or to replace the diseased segment as in livertransplantation.

The present invention proceeds from the realisation that this standardapproach is flawed. In many clinical or veterinary conditionsdemonstrating localised blood flow impedance, we believe that superiorresults may be achieved if instead of providing a surgical by-pass orother conventional treatment, means are adopted whereby blood flow isassisted through the area of impedance. This will generally result inlocalised hypertension, but the effects of this will not be feltsystemically. Replacing the diseased vessel containing the vascularimbalance (liver transplantation) is not a practical proposition on alarge scale because of the high cost of this procedure and because ofthe limited availability of donors.

According to one aspect of the present invention, there is provided amethod of improving the flow of blood through a region of increasedimpedance, which comprises assisting blood flow in the said region bymeans of a pump placed in or around a blood vessel supplying blood tosaid area, and acting to pump blood in the required direction.

The pump may be, for example, an Archimedes screw which acts directly onthe blood flowing within the vessel undergoing treatment, or it may be aperistaltic-type pump which acts on the outside of the vessel.

The invention will be described further with reference to treatment ofthe portal vein or hepatic pedicle (free edge of the lesser ormentum) toovercome problems arising from cirrhosis of the liver, although it is tobe understood that the invention is of general applicability and is notrestricted to this specific area of treatment.

The pump for use in this embodiment of the present invention can belocated internally within the portal vein, or it may be of a type (e.g.a peristaltic pump) which permits the motor to act on the exterior ofthe blood vessel, thereby avoiding the need to perform surgery on thevessel itself. Examples of suitable pumps will now be given.

In one arrangement, the pump is in the forth of an Archimedes screwwhich is located within a suitable prosthesis, e.g. one made of Dacron,which is inserted into or grafted between sections of the portal vein.Control of the screw can be achieved by means of a microprocessor housedunder the skin close to the site of the portal vein, or locatedexternally in a suitable housing which will generally be held close tothe body in the region of the portal vein. A pressure sensor may beincorporated in the screw pump, at the upstream end thereof, and may beincorporated into the control system; for example, the sensor can beused to ensure that the pressure in the portal vein is not greater than15 mm Hg. In order to avoid complications arising from thrombosis, theadministration of an anticoagulant may be desirable with thisarrangement.

A peristaltic pump acting on the outside of the hepatic portal vein isadvantageous in that its use requires less invasive surgery than theembodiment described above. In one arrangement, a conventional rolleraction is used to generate the peristaltic effect. As with theembodiment described above, control of the pump may be achievedelectrically using an externally located microprocessor.

An alternative peristaltic-type pump is also advantageous; this useshydraulic or pneumatic power to generate the required peristalticaction, and as above it can be controlled by an externally locatedmicroprocessor. One arrangement of this type utilises an annular sheathwhich conveys a compressive force along its length to assist blood flowwithin the vessel.

One embodiment of the peristaltic type comprises a jacket, sheath orcollar which, in use, surrounds the portal vein. In another embodiment,the peristaltic pump comprises a plurality of inflatable members whichare arranged to overlie the vessel or to sandwich it between them. Inboth embodiments, the device is advantageously under control of, forexample, a microprocessor. The fluid supply is preferably a pneumaticsupply, and can be provided via an air compressor located outside thebody of the patient. This may be at skin level close to the portal vein.A pressure sensor is preferably located on the surface of the portalvein and is linked to the microprocessor. When the pressure in that partof the portal vein between the pump and the liver exceeds 15 mm Hg, themicroprocessor will activate the air compressor and the pneumatic pumpaction. This will decrease the pressure within the part of the portalvein between the intestine and the pump, which in turn results incessation of bleeding from the oesophageal varices. Also, the pressurein the section of the portal vein between the device and the liver isincreased, thus leading to increased blood flow into the cirrhotic liverdespite the high resistance to blood flow. This in turn should assist inthe detoxification of blood before gastro-intestinal products reach thesystemic blood supply, thereby leading to an improvement in, orprevention of, hepatic encephalopathy.

According to a second aspect of the present invention, there is provideda pump adapted, at least by way of dimensioning and/or flow performancecharacteristics, for use in or around the hepatic portal vein to improvethe flow of blood therethrough against increased impedance caused byabnormality of the liver.

According to a third aspect of the present invention, there is providedthe use of a pump, locatable in or around a blood vessel, in themanufacture of a product for application in surgery to treat conditionscharacterised by impeded flow of blood through the liver.

Preferably, the blood vessel is the hepatic portal vein. Such a pump maycomprise a housing for annularly surrounding the hepatic portal vein,said housing containing a plurality of flexible inflatable containersmounted for contact with the hepatic portal vein and means for effectingsequential inflation and deflation of the containers so as to create aperistaltic pumping effect.

Preferably, a device of the type just described is divided into at leasttwo, and typically three annular segments or digitate elements each ofwhich has its own pneumatic supply, and is under individual controlfrom, for example, a microprocessor.

The jacket may be formed of two linked semilunar cusps which can be tiedat their edge to form an oblate cylindrical jacket which surrounds theovoid section of the portal vein. Such a shape is advantageous in thatpressure pulses applied via the jacket to the portal vein tend tocompress the two "sides" of the ovoid vein evenly. Also, application ofthe jacket to the portal vein at the free edge of the lesser ormentum issurgically very simple, as opposed to individual dissection of theportal vein. Preferably, the exterior surface of such a jacket issemi-solid, preferably silastic; and the inner surface (which contactsthe external wall of the portal vein in use) is membranous so as not todamage the tissue of the portal vein.

Where the jacket comprises three segments or elements, these can becontrolled so that each acts as a valve, permitting blood to flow in onedirection only. The three segments will be arranged to act sequentiallyin a predetermined manner so as to massage the portal vein on order todirect blood unidirectionally towards the liver. A variety of segmentalconfigurations and control arrangements are possible. For example, allthree segments may be substantially identical; or the middle segment maybe the largest. The control system either inflates or deflates thesegment (or cuff) to give the required control. It is presentlyenvisaged that a blood flow of up to 1.8 liter per minute from theportal vein into the liver should be possible by means of such a device.This may be contrasted with situations where, as a result of severecirrhosis, blood flow through the liver is actually reversed.

A presently preferred arrangement utilises three segments all of whichare of the same size. An operating sequence for such a three-segmentjacket is as follows, segment 1 being the most distal and segment 3 themost proximal with respect to the liver (i.e. segment 1 being downstreamand segment 3 being upstream with respect to the direction of flow ofblood towards the liver):

    ______________________________________                                                Time                                                                  Segment   t.sub.1   t.sub.2                                                                             t.sub.3 t.sub.4                                                                           t.sub.5                                 ______________________________________                                        1         I         I     D       D   I                                       2         D         I     I       D   D                                       3         D         D     I       D   D                                       ______________________________________                                         where I=inflated, and D=deflated. Other sequences are possible, provided     that unidirectionality of blood flow is maintained. The same sequence may     be used with three digitate elements instead of three annular cuffs.

It will thus be seen that compartment 1 (the distal segment) acts as avalve which allows blood to flow only towards the liver. When thissegment is inflated, the desired pumping action is achieved by inflatingthe central segment (segment 2) while the proximal segment 3 is stilldeflated. This action pumps blood towards the liver. Next, segment 3 isinflated- Then all three segments are deflated, after which segment 1 isinflated while segments 2 and 3 are deflated, thus priming the pump forthe next cycle. Since a device of this type involves minimal surgicalintervention, and does not involve any direct contact with the blood,the use of anticoagulants may not be needed.

It is envisaged that such a three-compartment jacket may be controlledso as to undergo about 60 cycles per minute, although it is preferredthat the pressure of operation and the frequency of operation be undermicroprocessor control. A device in accordance with this invention mayalso include one or more pressure sensors associated (in use) with theportal vein. Such sensors may be used to supply information to themicroprocessor which then controls the operation of the device inaccordance with prevailing pressure conditions in the portal vein.

A pneumatically operated embodiment such as that described above mayhave air supply lines for each segment of the jacket which pass throughthe body of a patient to the exterior, where they are connected to anair compressor. Since the jacket is entirely closed, there is no need touse purified air; the compressor can simply take ambient air and feedthis into the segments of the jacket.

A further feature of pneumatically operated jackets such as justdescribed is that operation of the jacket can be aborted in an emergencysimply by cutting the air supply line(s) from the compressor. Thisrepresents a considerable safety feature. Also, a sudden decrease inpressure in any one segment (which might be due to perforation of thesegment) wall lead to stoppage of the pump. Immediate cessation of pumpaction in such circumstances will prevent air being introduced into theperitoneal cavity.

In a further embodiment, a section of the portal vein is removed and isreplaced by a jacket which may be in the form described above withreference to an externally applied jacket. Alternatively, a singlecompartment annular prosthesis with a single air supply line may beused, but in conjunction with one-way valves at both ends of the jacket.With this arrangement, injection of air pumps blood forwards into theliver, and deflation allows blood to flow into the device from thesection of the portal vein between the intestine and the device. Becausethere is direct contact between the device and the blood, the use of ananticoagulant is preferred with this arrangement.

A device in accordance with this invention may be used by a patientcontinuously or intermittently; it may sometimes be advantageous tooperate the device for a period of, say, two, four or eight hours inevery twentyfour. In any case, such aspects will be decided inaccordance with advice from the patient's surgeon. Clinicalconsiderations will also be used to determine whether the device is leftin situ and used as and when required (both in relation to a diurnaloperating regime and in relation to longer term usage, e.g. operation ofthe device for four hours in every twentyfour for a period of fourteendays, followed by seven days without use). It may also be feasible toremove the device after a course of treatment, and to re-apply thedevice at a later date in the event of regression.

In one embodiment, the device uses a microprocessor and two pressuresensors to control its functioning. One sensor is located so as to sensethe prevailing pressure in that segment of the portal vein between thedevice and the intestines; and the second sensor so as to sense thepressure prevailing in that segment of the portal vein between thedevice and the liver. For example, if the pressure sensed by the firstsensor exceeds 15 mm Hg, the microprocessor will actuate the device;when this pressure falls below 15 mm Hg, the microprocessor will stopthe pump action of the device. Similarly, if the pressure sensed by thesecond sensor (between the device and the liver) exceeds 100 mm Hg, themicroprocessor will respond by switching off the pump action of thedevice, thereby overriding the control command resulting from the outputof the first sensor. This will prevent unacceptably high pressures inthe portal vein segment leading to the liver. Functioning of the pumpdevice will then be restored when the pressure sensed by the secondsensor falls below 100 mm Hg, provided that the pressure sensed by thefirst sensor exceeds 15 mm Hg. It will be appreciated that the pressuregiven above are by way of example only; the device of this invention ispreferably arranged so that it can be programmed to respond to anydesired limiting pressures in accordance with the surgeon's judgement.

This invention is expected to find application in other clinical orveterinary conditions involving increased impedance to blood flow, e.g.cardiac ischaemia and atherosclerosis of the renal artery, as well asischaemia of the limbs and brain, and pulmonary hypertension. It mayalso find use in the relief of ascites.

The action of the pump on the hepatic portal vein or hepatic pedicle(free edge of the lesser ormentum) in accordance with one aspect of thisinvention will cause a reduction in portal pressure and hence is likelyto relieve oesophageal varices. This reduction in portal pressure mayalso decrease bleeding in the splanchnic territory, which could be anadvantage in intestinal surgery.

For a better understanding of the invention and to show how the same maybe carried into effect, reference will now be made, by way of exampleonly, to the accompanying drawings, in which:

FIGS. 1a to c show a pump in accordance with the invention;

FIGS. 2.a to d show the constriction and dilation of the portal vein bya single active unit;

FIG. 3 shows a proposed sequence of dilation and constriction of theportal vein;

FIG. 4 shows schematically the control and power circuits in oneembodiment of the invention;

FIG. 5 shows a diagrammatic representation of apparatus used to definethe direction of flow of liquid when pumped by a pump in accordance withthe invention;

FIG. 6 shows a diagrammatic representation of apparatus used to definethe increase in portal pressure for an increase in output for a pump inaccordance with the invention;

FIG. 7 is a graph showing output against portal pressure for thesimulated hepatic bed, without action of a pump;

FIGS. 8a and b show chronographs and sequences of pressurisation andrelaxation of the SAS and ECHELON type cycles;

FIGS. 9a through d show chronographs of the SAS type cycle and threeECHELON type cycles tested on two pumps in accordance with one aspect ofthe invention;

FIGS. 10a and 10b are diagrams showing a comparison of the performancesof the SAS, ECH1, 2 and 3 cycles when tested on a pump in accordancewith one aspect of the invention;

FIG. 11 is a graph showing period of cycle against output for the twopumps tested;

FIGS. 12a and b are diagrams showing comparative performances of the twopumps tested;

FIG. 13 is a diagrammatic representation of the apparatus used to testthe pumps with simulated collateral branches; and

FIGS. 14a and b are diagrams showing comparative performances of the twopumps tested with a simulated collateral branch.

Referring first to FIG. 1, the pump 1 in accordance with the inventioncomprises a rigid casing 2 which annularly surrounds a vessel 3. Thevessel 3 contains a liquid which is to be pumped by the pump 1. Thecasing 2 may be constructed of a rigid transparent plastics material,and is divided into two sections (FIG. 1a) so that it may be placedaround the vessel 3. These two sections are then joined by means of aclip, bolt or other joining means. Housed inside the casing are two ormore, and in this case three, pairs of parallel, inflatable ballonets 4.These ballonets 4 are constructed of a flexible plastics material andare connected to a pressure supply (not shown) by means of conduits 5.The pressure supply may be pneumatic or hydraulic, although pneumaticpressure is preferred as it has a faster response time and the amount ofpower dissipated in heat is less.

As shown in FIG. 2, the pair of ballonets 4 lies either side of thevessel 3 so that pressure passing through conduit 5 and into a ballonetcauses inflation of the ballonets and hence constriction of the vessel3. Conversely release of pressure from the ballonet causes the vessel toregain is shape. The release of pressure may be passive or by means of avacuum pump.

The pump has two or more pairs of ballonets 4 so that sequentialinflation and deflation of each pair causes constriction of the vessel 3and hence pumping of the liquid contained therein (FIG. 3).

Referring now to FIG. 4, the means by which the pump 1 can be regulatedand controlled can be seen. Pressure generated by a compressor 7 isregulated by a pressure reducer 8 before entering the pump 1 viamicroelectrovalves 9. Deflation of the ballonets 4 is regulated by avacuum accumulator 10 which ensures stabilised constant deflation. Themicroelectrovalves control the flow of fluid and are themselves underthe control of a microprocessor 11 and a microcomputer/software 12. Themicrocomputer 12 is used to define the cycle of pressurisation and themicroprocessor 11 monitors the electrovalves 9 so that an accurate cycleis achieved. Indeed, the period of the cycle may be between 0.251seconds and 10 seconds with an accuracy of 1,000th of a second.

Inflation of the ballonets causes a progressive external compression ofthe vessel 3, and is hence particularly suited to assisting pumping offluid in vessels such as veins, ducts and arteries. The use of the pumphereinafter will be described with reference to the hepatic portal vein,although it is to be understood that the invention is of generalapplicability and is not restricted to this specific area of use. Asmentioned, the pump exerts a progressive external compression on avessel which avoids injury to the venous wall and total venous occlusionwhich may be harmful. In use, the ballonets may be oblique to the flowof blood, or may preferably be perpendicular thereto.

The properties of a pump as described above can be characterised on amodel of hepatic circulation. The portal vein is represented to scale bya conduit of flexible plastisol with an inner diameter of 20 mm and anouter diameter of 22 mm.

The performance of the pump is dependent on the following parameters:

    ______________________________________                                             ρ           density of liquid                                             μ            dynamic viscosity of liquid                                   g = 9.81 ms.sup.-2                                                                            acceleration in the field of gravity                          ΔQ.sub.v  change in output                                              ΔH        change in charge                                              ΔP = ρ · g · ΔH                                             change in pressure                                            R = ΔP/ΔQ.sub.v                                                                   hydraulic resistance; in a                                                    rigid conduit of diameter d                                                   and length l, for a Newtonian                                                 fluid in laminar flow regime                                                   ##STR1##                                                     P = ρ · g · ΔQ.sub.v  ·                  ΔH        useful power transferred by                              or   P = ΔQ.sub.v  · ΔP                                                       the accelerator to the flow.                             ______________________________________                                    

In the tests, water is used instead of blood because their densities (ρ)are very similar (water=1000 kg/m³, blood=1060 kg/m³). This similaritymeans that the transferred energy is substantially the same for bothliquids, but it is assumed that a) that output and hydraulic pressurehave the same nominal values as in physiological conditions, and b) thathydraulic and venous resistance are the same. Hence the hepatic vascularbed can be simulated to test the pump, although the effect of hepaticarterial circulation, the phenomena of compliance and of opening ofareas in the resistive bed, and the behaviour of non-Newtonian blood inthe capillaries cannot be simulated.

FIG. 5 shows diagrammatically apparatus used to define variouscharacteristics of the pump. In particular the direction of flow ofwater can be seen by the use of coloured liquid tracers injected intothe apparatus upstream of the pump and the output can be calculatedprecisely by the time taken to fill a standard volume.

The following describes experiments and results obtained in acomparative study of the performance of two pumps each with three pairsof ballonets but varying in their size, the first (A) being larger thanthe second (B). As mentioned, FIG. 5 shows diagrammatically apparatusused, in this case, to determine the direction of flow of water with andwithout the action of the pump. In Phase 0, without a pressure gradientbetween one end of the circuit and the other, the portal output(Q_(vpo)) is nil. With the pump functioning, as shown in Phase 1, waterflows towards the area of hepatic resistance (R_(hep)), despite theresistance to flow being greater in this direction.

FIG. 6 shows apparatus used to find by how much output is increased byaction of the pump. FIG. 7 shows how an increase in hepatic portalpressure H_(p) affects an increase in output Q_(v) without the pumpbeing used. H_(pav1) is the portal pressure which has to be generatedfor reestablishing output Q_(vp1) with the pump at rest.

Referring now to FIGS. 8a and b, the effectiveness of the SAS andECHELON type cycles can be assessed. As can be seen, the SAS cycleguarantees a one-way flow of liquid and prevents any backflow but hasthe disadvantage that it involves total venous occlusion, and hence therisk of venous wall damage. It also involves many sequences and can onlytransfer a low volume of liquid. The ECHELON type cycle cannot guaranteea prevention of backflow but propagates wave amplification without asmany sequences of inflation and deflation or the need for venousocclusion. Chronographs of the various cycles tested are shown in FIG.9, and FIG. 10a and 10b show a comparison of the performances of each ofthese cycles. As can be seen, the cycle ECH3 is more effective whateverthe H_(po) and R_(hep) values. This cycle has therefore been retainedfor a further study of the characteristics of the pump.

The optimum period of cycle T_(m), i.e. the length of time for acomplete cycle as shown in FIG. 8b, can be found by varying the periodof cycle T and examining the output Q_(vp). FIG. 11 shows how theoptimum period T_(m) can be found for both pumps 1 and 2 by plottingperiod of cycle T against output Q_(vp).

When T_(m) is defined, the optimum speed of compression can be found byusing the formula ##EQU1## where d is the distance between the centralaxes of the ballonets. For both pumps, C_(m) is virtually identical:##EQU2##

FIGS. 12a and b summarise the data contained in Table 1 below, for thetwo pumps tested on the simulation of hepatic circulation described.

                                      TABLE 1                                     __________________________________________________________________________             phase 1                                                              phase 0               ΔQ.sub.vp                                         H.sub.p0                                                                           Q.sub.vp0                                                                         Pump                                                                              Q.sub.vp1                                                                         ΔQ.sub.vp                                                                    Q.sub.vp0                                                                         H.sub.pAV1                                                                         ΔH                                                                          P                                          mm Hg                                                                              l/min                                                                             n*  l/min                                                                             l/min                                                                              %   mm Hg                                                                              mm Hg                                                                             mW                                         __________________________________________________________________________    10   0.65                                                                              1   1.12                                                                              0.47 72  20.4 10.4                                                                              11                                                  2   1.32                                                                               0.675                                                                             104 25.5 15.5                                                                                23.3                                     22   0.50                                                                              1   0.84                                                                              0.34 68  46.4 24.4                                                                              18                                                  2   0.80                                                                              0.30 60  41   19  13                                         __________________________________________________________________________

It can be seen that the increase in portal output ΔQ_(vp) and maximum oftransferred power P is obtained with low hypertension. AH, the excesspressure applied increases with the hypertension.

Pump No. 2 is most efficient with moderate hypertension, although pumpNo. 1 is more efficient at higher hypertension.

The performances of the two pumps may also be measured using asimulation of the collateral branch (simulating collateral circulationbetween the systemic and portal circulations). The apparatus used forthis may be seen in FIG. 13, where a branch with collateral resistanceR_(c) is placed upstream of the pump. The results for pumps 1 and 2 canbe seen both in Table 2 below and FIGS. 14a and 14b. Action the twopumps leads to increased portal output (ΔQ_(vp)), decreased portalpressure (ΔH) and decreased flow in the collateral (ΔQ_(vc)).

                                      TABLE 2                                     __________________________________________________________________________    phase 0             phase 1                                                   H.sub.p0                                                                          Q.sub.vp0                                                                         Pump                                                                              O.sub.vp0                                                                         ΔQ.sub.vc0                                                                  H.sub.p1                                                                          Q.sub.vs                                                                          Q.sub.vp1                                                                         Q.sub.vc1                                                                         ΔH                                                                          ΔQ.sub.vp                                                                   ΔQ.sub.vc                   mm Hg                                                                             l/min                                                                             n*  l/min                                                                             l/min                                                                             mm Hg                                                                             l/min                                                                             l/min                                                                             l/min                                                                             mm Hg                                                                             l/min                                                                             l/min                             __________________________________________________________________________    15  0.65                                                                              1   0.60                                                                              0.40                                                                              6.5 1   0.76                                                                              0.24                                                                              -8.5                                                                              +0.16                                                                             -0.16                                     2   0.64                                                                              0.36                                                                              5.9 1   0.81                                                                              0.19                                                                              -9.1                                                                              +0.17                                                                             -0.17                             22  0.50                                                                              1   0.48                                                                              0.52                                                                              9.2 1   0.71                                                                              0.29                                                                              -12.8                                                                             +0.23                                                                             -0.23                                     2   0.49                                                                              0.51                                                                              9.9 1   0.69                                                                              0.31                                                                              -12.1                                                                             +0.20                                                                              0.20                             __________________________________________________________________________

For both pumps the gain on portal output and decrease in portal pressureare accentuated with hypertension. Pump 2 is again more efficient atmoderate hypertension and pump 1 is more efficient with highhypertension. However the difference between the efficiencies is minimaland the performance of the two pumps in these tests is very similar.

The invention may be further illustrated by means of the followingexamples:

Our new hypothesis is that it is possible to reduce the portal pressurein the oesophageal varices by increasing the portal blood flow acrossthe cirrhotic liver. This would have the double advantage of preventingrebleeding without reducing the liver portal flow. To test thishypothesis we devised two experiments. The first (Example 1) was toinvestigate the relationship between portal pressure and liver portalflow in cirrhotic rat liver using the isolated liver perfusion model(Miller, L. L., Technique of liver perfusion. In: Bartosek, I., Guitani,A., Miller, L. L. eds. Isolated liver perfusion and its applications.New York: Raven Press, 1973: 11-52). The second (Example la) was toassess the ability of a newly designed pump to improve liver portal flowand reduce splanchnic portal pressure in pigs.

EXAMPLE 1

Liver cirrhosis was induced in Sprague-Dawley rats by IP injection of0.3 ml carbon tetrachloride in mineral oil, three times weekly for 8weeks. Two weeks following the last injection, the rats were submittedto laparotomy and the portal pressure was recorded by direct puncture ofthe portal vein. The livers were removed and placed in a modifiedisolated perfused system where the perfusion pressure varied from 0 to45 cm H₂ O. The perfusion solution was the oxygenated (O₂ 95% and CO₂5%), heated (37° C.) Krebs-albumin solution (pH 7.40±0.05). Thebase-line portal flow was measured for 20 minutes during which theportal pressure applied was equal to that measured in vivo prior to thesacrifice of the animal. The portal flow was then measured in the normaland cirrhotic livers over a period of 35 minutes. The portal flow wasmeasured for 15 minutes at a higher pressure of either 25 or 45 cm of H₂O. Cirrhosis was confirmed histologically. Statistical analyses weremade with the unpaired Student's t-test.

In the normal control rats (n=15), the base line portal pressure was10.3±0.67 cm of H₂ O. Subsequent increase of portal pressure to 25 cm ofH₂ O in 10 of these rats increased the portal flow from 3.38±0.86ml/min.gm⁻¹ to 6.25±1.2 ml/min.gm⁻¹ (P<0.001) while increase of portalpressure to 45 cm of H₂ O in the other 5 rats increased the portal flowfrom 2.23±0.42 ml/min.gm⁻¹ to 10.42±1.42 ml/min.gm⁻¹ (P<0.001).

In the cirrhotic rats (n=14), the base line portal pressure was13.1±2.41 cm of H₂ O. It was significantly (P<0.001) increased comparedto the baseline portal pressure in normal rats. Increase of portalpressure to 25 cm H₂ O in six of these rats increased the portal flowfrom 2.32±0.75 to 3.97±1.29 ml/min.gm⁻¹ (P>0.05) while increasing theportal pressure to 45 cm of H₂ 0 in the other four rats caused a rise inportal flow from 1.64±0.32 to 4.50±1.18 ml/min.gm⁻¹ (P<0.001).Histological examination of the normal and cirrhotic livers showed noparenchymal damage following increased portal pressure.

In the normal liver the doubling of portal pressure was associated witha doubling of portal flow (105% and 360% increase in portal pressure wasassociated with a 91% and 383% increase in portal flow respectively). Inthe cirrhotic liver, there was a similar direct relationship (i.e. 88%and 215% increase in portal pressure was associated with a 72% and 178%increase in portal flow respectively).

Therefore in both normal and cirrhotic liver, increase portal pressurewas associated with a significant increase in portal flow.

EXAMPLE 1a

Two 70 kg pigs were anaesthetized and submitted to laparotomy. Via abilateral subcostal incision the portal vein was dissected. The portalpressure was recorded with the insertion of a cannula in a jejunal vein.Another catheter was introduced via another jejunal vein and advancedbeyond the portal vein bifurcation. The portal flow was measuredcontinuously with Gould-Stratham 2202 flow meter using a probe placedaround the main left branch of the portal vein. Following this, thebranches of the portal vein were dissected. All the right and one leftsegmental portal branches were ligated. This raised the portal pressurein the first pig from 13 to 24 mm Hg and in the second pig from 12 to 23mm Hg. It also reduced the liver portal flow from 950 to 700 ml/min inthe first pig and from 650 to 180 ml/min in the second pig.

At this stage, a pump in accordance with one aspect of the presentinvention was applied around the portal vein. The pump consisted of anair driven pump composed of three pairs of balloons enveloped by a rigidbox. The three pairs worked in a cyclical sequence controlled bycomputer. The length, width and height of the balloon were 35 mm, 11 mmand 10 mm, respectively. The cycle duration was 0.8 second. The pressurein the balloons was generated with a compression-vacuum generator withan applied pressure of 0.32 bar.

Measurements of portal pressures and liver portal flow were repeated inboth pigs with successive applications of the pump. Statistical analysiswere made with paired t-test.

Five successive activations of the pump in the first pig reduced thesplanchnic portal pressure from 23.7±1.09 mm to 19.7±0.67 mm Hg(downstream of the pump) (P<0.01) and increased the portal pressureupstream of the pump from 23.88±0.54 mm to 31.24±2.54 mm Hg. This wasassociated with an increase in portal flow from 693±11 to 842±13 ml/min(P<0.001). In the second pig, activation of the pump reduced thesplanchnic portal pressure (downstream of the pump) from 21.75±1.5 to18.5±1.29 mm Hg and increased the portal pressure upstream to the pumpfrom 21.5±1.91 to 24.5±2.51 mm Hg (P<0.05). This was associated with anincrease in portal flow from 215±73 to 280±70 ml/min (P<0.001).

Our in vitro study shows that increased portal pressure leads toincreased portal flow. This was observed in both normal and cirrhoticliver using the isolated perfused model. Conventional histologicalexamination of these livers did not reveal any parenchymal damagefollowing brief periods of increased portal pressures.

In the reported in vivo experiments in pigs (Example 1a) with portalhypertension, the pump reduced the splanchnic portal pressure andsimultaneously increased the portal liver flow.

I claim:
 1. A method of treating the hepatic portal vein or hepaticpedicle to improve the blood flow therethrough against increasedimpedance caused by abnormality of the liver, said method comprising thesteps of:placing a pump in communication with the hepatic portal vein orhepatic pedicle; and actuating said pump to improve blood flow throughsaid hepatic portal vein or hepatic pedicle and thereby improve bloodflow through the liver.
 2. A method as claimed in claim 1, wherein saidpump is an Archimedes screw pump.
 3. A method as claimed in claim 1,wherein said pump is a peristaltic-type pump.
 4. A method as claimed inclaim 2, wherein said Archimedes screw pump is located within aprosthesis which is inserted into or grafted between sections of saidhepatic portal vein.
 5. A method as claimed claim 3, wherein saidperistaltic-type pump generates its peristaltic effect by a rolleraction.
 6. A method as claimed claim 3, wherein said peristaltic-typepump uses hydraulic or pneumatic power to generate its peristalticeffect.
 7. A method as claimed in claim 6, wherein said peristaltic typepump uses pneumatic power provided via an air compressor located outsidethe body of the patient.
 8. A method as claimed claim 6, wherein saidperistaltic-type pump comprises a jacket, sheath or collar whichsurrounds said hepatic portal vein.
 9. A method as claimed in claim 8,wherein said jacket, sheath or collar is divided into three annularcompartments, and wherein each of said compartments is suppliedindependently with its own pneumatic or hydraulic supply.
 10. A methodas claimed in claim 9, wherein said compartments are inflated anddeflated sequentially as shown by the following table, compartment 1being the distal and compartment 3 being the most proximal with respectto said area of impedance, D indicating deflation and I indicatinginflation:

    ______________________________________                                                 Time                                                                 Compartment                                                                              t.sub.1   t.sub.2                                                                             t.sub.3 t.sub.4                                                                           t.sub.5                                ______________________________________                                        1          I         I     D       D   I                                      2          D         I     I       D   D                                      3          D         D     I       D   D                                      ______________________________________                                    


11. A method as claimed in claim 1, wherein a section of said bloodvessel is removed and replaced by a jacket, sheath or collar, and bloodis caused to flow by the combination of inflation of said jacket, sheathor collar and one-way valves at both ends of the jacket.
 12. A method asclaimed in claim 1, wherein operation of said pump is controlled by amicroprocessor.
 13. A method as claimed in claim 12, wherein saidmicroprocessor is located at skin level close to the site of the bloodvessel.
 14. A method as claimed in claim 12, wherein said microprocessoris located externally in a housing.
 15. A method as claimed in claim 1,wherein the pressure in said blood vessel either side of said pump ismonitored by means of first and second sensors, said first sensor beinglocated so as to sense the prevailing pressure in that segment of saidblood vessel upstream of said pump and said second sensor being locatedso as to sense the prevailing pressure in that segment of said bloodvessel downstream of said pump.
 16. A method as claimed in claim 15,wherein said first and second sensors are connected to saidmicroprocessor so as to control the action of said pump within presetpressure limits.
 17. A method as claimed in claim 1, wherein saidabnormality of the liver is cirrhosis of the liver, liver insufficiencyor atherosclerosis of the renal artery.
 18. A method as claimed in claim2, wherein said pump is housed in a prosthesis which is inserted intothe hepatic portal vein.
 19. A method as claimed in claim 2, whereinsaid pump is housed in a prosthesis which is grafted between sections ofthe hepatic portal vein.
 20. A method as claimed in claim 1, whereinsaid pump is placed in or around the hepatic portal vein or hepaticpedicle.
 21. A method as claimed in claim 1, wherein said pump comprisesa housing means for annularly surrounding said hepatic portal vein, saidhousing means containing a plurality of flexible, inflatable containersmounted for contact with said hepatic portal vein and means foreffecting sequential inflation and deflation of said containers so as tocreate a peristaltic pumping effect.
 22. A method as claimed in claim21, wherein said housing means is divided parallel to the direction ofsaid flow of blood so that it, may be placed around said hepatic portalvein.
 23. A method as claimed in claim 21, wherein said means forsequential inflation and deflation comprises a pressure source, apressure regulator, a microprocessor and a microcomputer.
 24. A methodas claimed in claim 23, wherein said means for sequential inflation anddeflation further comprises microelectro valves.
 25. A method as claimedin claim 22, wherein said housing means is formed of a substantiallyrigid plastic material.
 26. A method as claimed in claim 21, whereinsaid containers are formed of a substantially extendable plasticmaterial.
 27. A method as claimed in claim 21, wherein said containerslie parallel to one another and perpendicular to the direction of saidblood flow.